Most proteins destined for the periplasm or the outer membrane of gram negative bacteria, such as enteric bacteria, are transported across the cytoplasmic membrane by the general secretory pathway or Sec system, a complex of proteins, which identifies polypeptides for export and translocates them across the cytoplasmic membrane. This system has been used to secrete mammalian proteins from the enteric bacteria E. coli, including antibody fragments. Natural prokaryotic secreted proteins and heterologous proteins such as mammalian proteins are directed to the secretory apparatus by the addition of a functional signal peptide, a sequence of typically between 13 and 30 amino acids at the N-terminus of the protein which has a hydrophobic core and additional sequences to direct the nascent polypeptide chain to the secretory apparatus and allow accurate removal of the signal peptide after secretion. A number of prokaryotic signal peptides have been described which allow efficient secretion of at least some antibody fragments, including the signal peptides from the Erwinia caratovora pectate lyase B (PelB) protein, Escherichia coli heat-stable enterotoxin (StII) and the E. coli OmpA protein. Other prokaryotes have similar secretory systems, and signal peptides have been described for many for these other prokaryotes.
However, secretion systems are highly variable in the efficiency with which antibodies, antibody fragments or antibody-related polypeptides are secreted. The efficiency of secretion is dependent on the sequence of the variable regions of both the heavy and the light chains of antibodies. For example, Fab fragments containing murine V-regions are poorly secreted if at all. Further, human Fab fragments are secreted with variable efficiency, depending on the V-region sequence, and/or VH subclass. Such variable secretion efficiency leads to bias in the sequences of antibodies which may be screened from a generated antibody library.
In some cases, mutations in the V-region can be introduced in order to improve secretion. However, alterations in the amino acid sequence of antibody V-regions may compromise antibody function and are not generally desirable.
Furthermore, cleavage of signal peptides from the secreted polypeptide is not always efficient. For example, the signal peptide of E. coli OmpA or PhoA is not cleaved from a fusion protein with human interleukin-1 beta (IL-1 beta) when the fusion protein is expressed in E. coli. 
It is an object of the present invention to provide compositions and methods for obtaining secretion of antibodies, antibody fragments, or antibody-related polypeptides from bacteria without the need for a signal sequence thereby removing any secretion constraints caused by variable region sequence.